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中药解毒方通过调控Smad2/3依赖和非依赖途径抑制肝癌上皮-间质转化

The Chinese Medicine, Jiedu Recipe, Inhibits the Epithelial Mesenchymal Transition of Hepatocellular Carcinoma via the Regulation of Smad2/3 Dependent and Independent Pathways.

作者信息

Liang Shufang, Zou Yong, Gao Jingdong, Liu Xiaolin, Lin Wanfu, Yin Zifei, Du Juan, Zhang Ya'ni, Chen Qunwei, Li Shu, Cheng Binbin, Ling Changquan

机构信息

Department of Traditional Chinese Medicine, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.

Department of Oncology, Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu 215009, China.

出版信息

Evid Based Complement Alternat Med. 2018 Aug 8;2018:5629304. doi: 10.1155/2018/5629304. eCollection 2018.

DOI:10.1155/2018/5629304
PMID:30174709
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6106903/
Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. In China, traditional Chinese herb medicine has been widely used in the treatment of HCC. Jiedu Recipe (JR) is a common used prescription which has shown good results against HCC. However, the exact mechanisms of JR are still unknown. Therefore, we investigated the efficacy of JR on HCC in the current study. JR inhibited the cell viability of both SMMC-7721 and Huh7 cells in both time- and dose-dependent manners. Transwell assay revealed that JR decreased the number of migrated cells of SMMC-7721 cells. JR treatment increased the E-cadherin expression level and decreased the levels of p-Smad2/3 and Smad2/3. Further study showed that JR reversed the effect of TGF1 on the expression of E-cadherin, vimentin, N-cadherin, and MMP2/9. JR also significantly inhibited TGF1-induced migration and invasion of SMMC-7721 and Huh7 cells determined by wound healing assay and transwell assay. TGF1 treatment increased the phosphorylation of Smad2/3, p38 MAPK, JNK, ERK1/2, and Akt in SMMC-7721 cells and pretreatment with JR blocked TGF1-induced activation of Smad2/3 and Akt and MAPKs. In conclusion, JR inhibits liver cancer cells migration and invasion through epithelial mesenchymal transition (EMT) inhibition via Smad2/3 dependent and independent pathways, suggesting it is an effective therapeutic strategy against HCC metastasis.

摘要

肝细胞癌（HCC）是全球最常见的恶性肿瘤之一。在中国，传统中药已广泛用于HCC的治疗。解毒方（JR）是一种常用方剂，已显示出对HCC有良好疗效。然而，JR的确切作用机制仍不清楚。因此，我们在本研究中探讨了JR对HCC的疗效。JR以时间和剂量依赖性方式抑制SMMC-7721和Huh7细胞的细胞活力。Transwell实验表明，JR减少了SMMC-7721细胞的迁移细胞数量。JR处理增加了E-钙黏蛋白的表达水平，并降低了p-Smad2/3和Smad2/3的水平。进一步研究表明，JR逆转了TGF1对E-钙黏蛋白、波形蛋白、N-钙黏蛋白和MMP2/9表达的影响。通过伤口愈合实验和Transwell实验确定，JR还显著抑制了TGF1诱导的SMMC-7721和Huh7细胞的迁移和侵袭。TGF1处理增加了SMMC-7721细胞中Smad2/3、p38 MAPK、JNK、ERK1/2和Akt的磷酸化，而JR预处理则阻断了TGF1诱导的Smad2/3、Akt和MAPKs的激活。总之，JR通过Smad2/3依赖性和非依赖性途径抑制上皮-间质转化（EMT），从而抑制肝癌细胞的迁移和侵袭，表明它是一种对抗HCC转移的有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/07323c9da967/ECAM2018-5629304.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/9423e6b50cd1/ECAM2018-5629304.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/a6fa62ffeab4/ECAM2018-5629304.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/90111cb49ba2/ECAM2018-5629304.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/b1ff2c68b820/ECAM2018-5629304.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/07323c9da967/ECAM2018-5629304.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/9423e6b50cd1/ECAM2018-5629304.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/a6fa62ffeab4/ECAM2018-5629304.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/90111cb49ba2/ECAM2018-5629304.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/b1ff2c68b820/ECAM2018-5629304.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a884/6106903/07323c9da967/ECAM2018-5629304.005.jpg

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